ABSTRACT Stem cell-based platforms have transformed our understanding of many nervous system disorders, such as epilepsy. However, neurons develop in a highly complex environment of an intact brain, and functional maturation in vitro may not accurately reflect the developmental processes occurring in vivo. To accurately recapitulate the early developmental stages of synaptic and neuronal network dysfunction in these patients, direct access to patient neurons in an in vivo microenvironment is indispensable. Here, we propose an innovative approach to evaluate the in vivo development and function of neurons differentiated from human induced pluripotent stem cells. To accomplish this goal, we will develop a stem cell transplantation strategy to graft forebrain neurons into the developing brain. Using cell type-specific markers to fluorescently label subsets of neurons and a series of ex vivo and in vivo assays, we will record neuronal, synaptic and circuit-level properties of both the grafted and native-born neurons simultaneously for days to weeks. If successful, our work will provide an entirely new platform for studying epilepsy and other human nervous system disorders, one that would allow investigators to systematically and comprehensively evaluate how patient neurons become fully, and correctly, integrated into the developing brain circuitry and how they function in real time during behavior. It will also form the basis from which we can test emerging therapies on transplanted patient neurons.